关于壳聚糖材料生物相容性机制的新观点

目的：近年来,壳聚糖作为组织工程支架得到广泛应用,本文总结了壳聚糖生物相容性研究进展,提出细胞与壳聚糖相互作用可能机制的猜想,并对证实该猜想的试验模型进行初步探讨。资料来源：用计算机检索Medline,Pubmed和Elsevier数据库1998-01/2006-12与壳聚糖生物相容性研究相关的文章,检索词为“chitosan,biocompatibility,surface charge,cell adhesion”,并限定文章语言种类为English。资料选择：对资料进行初审,纳入标准：①选择与壳聚糖生物相容性,壳聚糖和细胞相互作用有关的文章。②着重关注研究壳聚糖表面电荷对细胞粘附影响的文献。排除标准：重复研究。资料提炼：共搜集到374篇相关文献,对其中入选的30篇文献进行归纳和分析。资料综合：多种哺乳动物细胞能够在壳聚糖材料上粘附、铺展、增殖,部分学者认为这是由于壳聚糖材料上氨基带正电,因此和带负电的细胞之间存在静电吸引作用造成的。然而实验结果表明,壳聚糖链上氨基的pKa值在6.2～6.8之间,因此在生理条件下壳聚糖材料表面的大部分氨基会去质子化,从而造成壳聚糖所带正电荷相对于酸性条件时大幅度下降。基于此,作者认为壳聚糖的生物相容性是否由其正电荷引起还需要深入研究。结论：结合已有的研究结果,提出猜想：正电荷可能不是导致壳聚糖材料生物相容性的主要因素。同时认为琼脂糖/壳聚糖混合水凝胶可能是验证此猜想的有效模型。

Mechanisms for biocompatibility of chitosan: A new viewpoint

OBJECTIVE:In recent years, chitosan has been widely used as tissue engineering scaffolds. In this paper we reviewed the research progress in chitosan biocompatibility and gave a hypothesison possible mechanism of interactions between cells and chitosan. A model system to test this hypothesis was also discussed. DATA SOURCES: Literatures about chitosan biocompatibility were retrieved with computer in Medline, Pubmed and Elsevier from January 1998 to December 2006 with the key words of."chitosan, biocompatibility, surface charge, cell adhesion" in English.STUDY SELECTION: Literatures about chitosan biocompatibility and interactions between chitosan and cells, especially the influence of chitosan charges on cell attachment, were included, whereas repeated experiments were excluded.DATA EXTRACTION: Totally 374 literatures were collected. Among which, 30 were admitted and reviewed.DATA SYNTHESIS: Many mammalian cells can adhere, spread and proliferate on chitosan materials. It is widely accepted that the biocompatibility of chitosan is due to the electrostatic attractive force between positively charged amino groups on chitosan chains and negatively charged cell membranes. However, the pKa value of chitosan amino groups is 6.2-6.8 and the positive charge of chitosan chains is largely decreased under physiological condition as a result of amino groups unprotonation. Thus whether the chitosan's biocompatibility is due to its positive charge remains doubtful and needs further study.CONCLUSION: Based on prior studies, we hypothesize that the positive charge of amino groups on chitosan chains might not be the major factor in biocompatibility of chitosan material. Agarose/chitosan blending hydrogels is supposed to be an appropriate model system to test this hypothesis.